The role that cross-reactive antibodies play in the pathogenesis of rheumatic valvular heart disease will be investigated. The basis for the cross-reactivity of antibody to the group A streptococcal group - specific carbohydrate and a glycopeptide component of heart valve tissue will be studied. Using a model devised for demonstrating the cytotoxic effect of specific antibody to valvular and myocardial tissue in-vitro, antisera to various components of the group A streptococcus will be tested for cytotoxic effect. The role of cell-mediated immunity to various streptococcal antigens in the pathogenesis of rheumatic carditis will be investigated. The basis of susceptibility to rheumatic fever will be investigated. Differences between rheumatic and non-rheumatic individuals in the processing of streptococcal antigens by the host, in the type of immune response (humoral or cellular) to the streptococcal infection will be looked for. Immunochemical studies on cardiac valves obtained from rheumatic and non-rheumatic individuals will be performed and differences in the susceptibility of the valves to the cytotoxic effect of streptococcal antibody will be examined.